Determining Causes of Insulin-Induced Hypoglycemia Using an Electronic-Based Trigger.

Injection of botulinum toxin A for the treatment of dysfunction of the upper esophageal sphincter

Nursing and midwifery management of hypoglycaemia in healthy term neonates

The primary objective of this review was to determine the best available evidence for maintenance of euglycaemia in healthy term neonates, and the management of asymptomatic hypoglycaemia in otherwise healthy term neonates.The review included any relevant published or unpublished studies undertaken between 1995 and 2004. Studies that focus on the diagnostic accuracy of point-of-care devices for blood glucose screening and/or monitoring in the neonate were initially included as a subgroup of this review. However, the technical nature and complexity of the statistical information published in diagnostic studies retrieved during the literature search stage, as well as the considerable volume of published research in this area, suggested that it would be more feasible to analyse diagnostic studies in a separate systematic review.The review focused on studies that included healthy term (37- to 42-week gestation) appropriate size for gestational age neonates in the first 72 h after birth.All interventions that fell within the scope of practice of a midwife/nurse were included:Interventions that required initiation by a medical practitioner were excluded from the review.Outcomes that were of interest included:The review initially focused on randomised controlled trials reported from 1995 to 2004. Insufficient randomised controlled trials were identified and the review was expanded to include additional cohort and cross-sectional studies for possible inclusion in a narrative summary.The major electronic databases, including MEDLINE/PubMed, CINAHL, EMBASE, LILACS, Cochrane Library, etc., were searched using accepted search techniques to identify relevant published and unpublished studies undertaken between 1995 and 2004. Efforts were made to locate any relevant unpublished materials, such as conference papers, research reports and dissertations. Printed journals were hand-searched and reference lists checked for potentially useful research. The year 1995 was selected as the starting point in order to identify any research that had not been included in the World Health Organisation review, which covered literature published up to 1996. The search was not limited to English language studies.Three primary reviewers conducted the review assisted by a review panel. The review panel was comprised of nine nurses with expertise in neonatal care drawn from senior staff in several metropolitan neonatal units and education programs. Authorship of journal articles was not concealed from the reviewers. Methodological quality of each study that met the inclusion criteria was assessed by two reviewers, using a quality assessment checklist developed for the review. Disagreements between reviewers were resolved through discussion or with the assistance of a third reviewer.Two reviewers used a data extraction form to independently extract data relating to the study design, setting and participants; study focus and intervention(s); and measurements and outcomes.As only one relevant randomised controlled trial was found, a meta-analysis could not be conducted nor tables constructed to illustrate comparisons between studies. Instead, the findings were summarised by a narrative identifying any relevant findings that emerged from the data.Seven studies met the inclusion criteria for the objective of this systematic review. The review provided information on the effectiveness of three categories of intervention - type of feeds, timing of feeds and thermoregulation on two of the outcome measures identified in the review protocol - prevention of hypoglycaemia, and re-establishment and maintenance of blood or plasma glucose levels above the set threshold (as determined by the particular study). There was no evidence available on which to base conclusions for effectiveness of monitoring or developmental outcomes, and insufficient evidence for breast-feeding success.Given that only a narrative review was possible, the findings of this review should be interpreted with caution. The findings suggest that the incidence of hypoglycaemia in healthy, breast-fed term infants of appropriate size for gestational age is uncommon and routine screening of these infants is not indicated. The method and timing of early feeding has little or no influence on the neonatal blood glucose measurement at 1 h in normal term babies. In healthy, breast-fed term infants the initiation and timing of feeds in the first 6 h of life has no significant influence on plasma glucose levels. The colostrum of primiparous mothers provides sufficient nutrition for the infant in the first 24 h after birth, and supplemental feeds or extra water is unnecessary.Skin-to-skin contact appears to provide an optimal environment for fetal to neonatal adaptation after birth and can help to maintain body temperature and adequate blood glucose levels in healthy term newborn infants, as well as providing an ideal opportunity to establish early bonding behaviours.The seven studies analysed in this review confirm the World Health Organisation's first three recommendations for prevention and management of asymptomatic hypoglycaemia, namely:1 Early and exclusive breast-feeding is safe to meet the nutritional needs of healthy term newborns worldwide.2 Healthy term newborns that are breast-fed on demand need not have their blood glucose routinely checked and need no supplementary foods or fluids.3 Healthy term newborns do not develop 'symptomatic' hypoglycaemia as a result of simple underfeeding. If an infant develops signs suggesting hypoglycaemia, look for an underlying condition. Detection and treatment of the cause are as important as correction of the blood glucose level.If there are any concerns that the newborn infant might be hypoglycaemic it should be given another feed. Given the importance of thermoregulation, skin-to-skin contact should be promoted and 'kangaroo care' encouraged in the first 24 h after birth. While it is important to main the infant's body temperature care should be taken to ensure that the child does not become overheated.

152: Glucose control in a surgical intensive care unit after orthotopic liver transplantation

This prospective, open study was carried out in order to assess changes in the swallowing and dietary status after injection of Botulinum toxin A (BoNT-A) into the upper esophageal sphincter (UES) in a series of patients with cricopharyngeus (CP) muscle dysfunction associated with pharyngo-laryngeal weakness during at least 1 year follow-up after treatment. Patients who had a cricopharyngeus (CP) muscle dysfunction associated with pharyngo-laryngeal weakness and who were at risk for aspiration were included in the study. The upper border of the cricoid cartilage was identified and the CP muscle localized using a standard electromyogram (EMG). The dose of BoNT-A was determined depending on the results of EMG performed just before the injection. Outcomes were assessed by the penetration-aspiration scale (PAS), the level of residue in the pyriform sinus and the National Institute of Health-Swallow Safety Scale (NIH-SSS) on a video fluoroscopic swallowing (VFSS) assessment, the patient's subjective impressions of their ability to swallow by the Deglutition Handicap Index (DHI), and changes in dietary status by the Functional Oral Intake Scale. Eleven patients underwent the complete assessment of swallowing function at 1, 3, 6, and 12 months. After the first set of treatment, seven patients had a good response and four did not respond. A significant decrease in the PAS score (p = 0.03), the amount of residue (p = 0.04) and the NIH-SSS score (p = 0.03) was observed 3 months after the injection in comparison with the first VFSS before the treatment. A relapse of dysphagia occurred in 3 out of the 11 treated patients; at 3 and 4 months for 2 patients with a Wallenberg syndrome, and at 11 months for a patient with cranial nerve paralysis after a surgery for a glomus tumor. Two of them underwent a second injection. One patient had a good response and remained stable for at least 1 year. The second did not respond either to the second injection or to a myotomy of the cricopharyngeal muscle. The third one is waiting for further surgery (myotomy). Therefore, at the end of the study and after a follow-up of at least 12 months, 5 patients out of the 11 enrolled had a good result. Percutaneous injection of BoNT-A into the UES can be a useful solution to improve cricopharyngeal dysfunction, despite the underlying pharyngo-laryngeal weakness.

Hypoglycemia, defined as a blood glucose level <70 mg/dL (3.9 mmol/L), occurs frequently in hospitalized patients. Both inpatient and outpatient trials have shown that the risk of hypoglycemia limits the achievement of blood glucose control (1–7). In addition to causing distress for patients, severe hypoglycemia is associated with cardiac arrhythmias, cardiac ischemia, seizures, brain damage, and death (3,4,8–12). After a hypoglycemic event, the likelihood of further episodes of low blood glucose is increased (2,9,12,13). Glycemic variability is also independently associated with risk of mortality (5–9,12,14,15) and can be an unintended consequence of reactive treatment of hypoglycemia. If dextrose is given only in response to low blood glucose levels, but the precipitating factor for hypoglycemia persists, a cycle of recurrent low glucose levels alternating with higher post-treatment levels occurs. Fortunately, this pattern represents a modifiable risk, as illustrated in Figure 1 (14). FIGURE 1. Recurrent hypoglycemia: treatment versus prevention. Initially hypoglycemia was treated reactively, with at least five recurrences of low blood glucose and high glycemic variability. With initiation of proactive IV dextrose, further hypoglycemia was prevented, and glycemic variability was reduced. Recent advances in health care quality and patient safety call for a change from reactive to preventive care. When this concept is applied to hypoglycemia management, it is evident that the unevaluated assumption that reactive treatment of hypoglycemia is sufficient often underlies facility routines. Avoiding circumstances that are frequently associated with low blood glucose levels is at the core of optimal glycemic management in the inpatient setting. Recent studies show that “safe and effective glucose control” (15) can be facilitated and hypoglycemia can be prevented through tactics such as appropriate monitoring, ensuring adequate caloric intake, coordinating the …

Although the ability of isolated frog muscle to synthesize glycogen from lactate has long been known, it has never been demonstrated that this metabolic activity occurs in the intact frog. Our results clearly indicate that lactate glycogenesis in frog muscle occurs to a significant extent in vivo. During recovery from strenuous exercise, most of the lactate accumulated by frogs seems to be recycled into muscle glycogen because the lactate that disappears during recovery could account nearly stoichiometrically for the glycogen that accumulates in muscle. Furthermore, the decrease in body lactate and the increase in muscle glycogen follow corresponding time courses, suggesting a precursor-product relationship between lactate and glycogen. During recovery from intense exercise, hepatectomized and normal frogs have nearly identical extents of lactate elimination and glycogen synthesis. This suggests that muscle is the main tissue responsible for the recycling of lactate into muscle glycogen and that liver plays a negligible role in lactate disposal. The negligible hepatic contribution to lactate recycling results in part from the liver's incapacity to produce glucose from lactate. In support of this proposition, we show that frog liver perfused in vitro is unable to incorporate any detectable labeled lactate into glucose despite its excellent physiological integrity. Changes in dietary status, training state, season at which the experiments were done, exercise status, and composition of the perfusion media (pH, hormonal composition, physiological saline vs. culture medium) did not give rise to lactate gluconeogenesis. Because frog liver contains all the regulatory enzymes of the gluconeogenic pathway, its inability to synthesize glucose from lactate is not due to an absence of pyruvate carboxylase. A limited ability for lactate uptake may explain why frog liver cannot produce glucose from lactate.

The immunological and catalytically active form of L-type pyruvate kinase in rat liver cytosol

Richard Winfield Hanson (1936–2014)

BackgroundHepatic fatty acids (FAs) are modified through different metabolic pathways including elongation and desaturation. These processes are catalyzed by elongases and desaturases, respectively. Glucose, by transcription factors, regulates these processes. The aim of the study was to evaluate the influence of high carbohydrate diet (68%) on the expression of elongase (Elovl-2, Elovl-5, and Elovl-6) and desaturase (∆5D, ∆6D, Scd 1, Scd 2) genes and the activity of the enzymes. The changes in serum lipid profile (triglycerides (TG), total cholesterol (TC), HDL cholesterol) and glucose concentration were measured. Male Wistar rats were randomized into two study groups: animals fed with high carbohydrate diet (n = 6; HiCHO) and a control group fed with a standard diet (n = 6; ST). The expression of mRNA was determinate using reverse transcription PCR (RT-PCR). Hepatic FA composition was determined by gas chromatography, and FA ratios were used to estimate the activity of enzymes. Serum lipid profile and glucose concentration were measured using spectrophotometric methods.ResultsThe mean values of transcript expression of all examined elongases and desaturases in liver HiCHO rats were higher as compared to ST. Higher expression did not always correspond to higher activity (as index). More monounsaturated FAs (MUFAs) were detected in the liver of HiCHO rats as compared to ST. Serum TG level was higher in the HiCHO than in ST.ConclusionsThese studies support the notion that the regulation of both Elovl and desaturase expression may play an important role in managing hepatic lipid composition in response to changes in dietary status.

An experiment was conducted to determine if changes in the level of dietary amino acids fed to laying hens as a single amino acid or a natural protein reflected on changes in plasma amino acid content.A basal diet was formulated in which all essential amino acids were not less than NRC requirements. A high-protein diet was made with the addition of 10% fish meal to the basal diet, and a high-valine diet was made by the addition of 0.3% valine to the basal diet.The concentrations of eight plasma amino acids (threonine, valine, methionine and cystine, isoleucine, leucine, lysine, and arginine) increased within 7 days and thereafter remained constant on the high-protein diet. But those of five amino acids (serine, glutamic acid, alanine, tyrosine, and phenylalanine) were kept constant throughout the experiment. On the valine diet, the concentration of plasma valine increased until 14 days, but those of other amino acids remained constant.The data suggests that plasma amino acids levels may serve as a more effective and rapid evaluation of changes in dietary status than a long term feeding test.

Background: Continuous glucose monitoring (CGM) provides real-time glucose levels and alarms for hypoglycemia. We analyze CGM data from the REPLACE-BG trial, which had 6 months of CGM data on people with well controlled type 1 diabetes (T1D), to characterize hypoglycemic events and evaluate their association with hypoglycemia-related behaviors. Methods: We conducted a psychometric analysis of the Hypoglycemia Fear Survey- Behavior scale to identify unique hypoglycemia behavior constructs. We identified and categorized hypoglycemic events in CGM data as mild (min glucose &amp;lt;70 mg/dL) and moderate (min glucose &amp;lt;50 mg/dL) and used ANOVA to evaluate differences in the frequency and duration of events by high and low score categories of hypoglycemia behavior constructs. We used multivariate linear regression to evaluate the association between hypoglycemia behavior constructs and 1) duration of moderate hypoglycemic events and 2) proportion of moderate hypoglycemic events. Results: We separated the HFS-B into three scales: hypoglycemia avoidance, reaction, and prevention. In low vs. high hypoglycemia prevention score categories, the duration of moderate hypoglycemic events was significantly longer (73 vs. 66 minutes, p&amp;lt;0.05) and proportion of moderate hypoglycemic events was higher (22.4 vs. 20.1, p&amp;lt;0.1). In multivariate models that included all three hypoglycemia behavior scales, hypoglycemia prevention behavior was significantly, inversely associated with 1) duration of moderate hypoglycemic events (β= -6.9, SE= 2.2, p&amp;lt; 0.01) and 2) proportion of moderate hypoglycemic events (β= -2.2, SE= 0.7, p-value &amp;lt; 0.01). Conclusion: Hypoglycemia is common in T1Ds. The increased likelihood of engaging in hypoglycemia prevention behaviors reduces the frequency and duration of dangerous moderate hypoglycemic events. Analyzing CGM data in its continuous form reveals the frequency and characteristics of individual hypoglycemic events. Disclosure M.A. Crawford: Employee; Self; Dexcom, Inc. M.M. White: None. D.R. Strong: None. J.P. Pierce: None.

BackgroundHypoglycaemia is a common and potentially avoidable adverse event in people with type 2 diabetes (T2D). It can reduce quality of life, increase healthcare costs, and reduce treatment success. We investigated self-management issues associated with hypoglycaemia and self-identified causes of hypoglycaemia in these patients.MethodsIn this mixed methods study qualitative semi-structured interviews were performed, which informed a subsequent quantitative survey in T2D patients. All interviews were audio recorded, transcribed verbatim and coded independently by two coders using directed content analysis, guided by the Theoretical Domains Framework. Descriptive statistics were used to quantify the self-management issues and causes of hypoglycaemia collected in the survey for the respondents that had experienced at least one hypoglycaemic event in the past.ResultsSixteen participants were interviewed, aged 59–84 years. Participants perceived difficulties in managing deviations from routine, and they sometimes lacked procedural knowledge to adjust medication, nutrition or physical activity to manage their glucose levels. Grief and loss of support due to the loss of a partner interfered with self-management and lead to hypoglycaemic events. Work ethic lead some participant to overexerting themselves, which in turn lead to hypoglycaemic events. The participants had difficulties preventing hypoglycaemic events, because they did not know the cause, suffered from impaired hypoglycaemia awareness and/or did not want to regularly measure their blood glucose. When they did recognise a cause, they identified issues with nutrition, physical activity, stress or medication. In total, 40% of respondents reported regular stress as an issue, 24% reported that they regularly overestimated their physical abilities, and 22% indicated they did not always know how to adjust their medication. Around 16% of patients could not always remember whether they took their medication, and 42% always took their medication at regular times. Among the 83 respondents with at least one hypoglycaemic event, common causes for hypoglycaemia mentioned were related to physical activity (67%), low food intake (52%), deviations from routine (35%) and emotional burden (28%). Accidental overuse of medication was reported by 10%.ConclusionPeople with T2D experience various issues with self-managing their glucose levels. This study underlines the importance of daily routine and being able to adjust medication in relation to more physical activity or less food intake as well as the ability to reduce and manage stress to prevent hypoglycaemic events.

Optimal inpatient glycemic management targets a blood glucose (BG) of 140-180 mg/dL and is an important safety measure for hospitalized patients with hyperglycemia. Traditional barriers to appropriate insulin administration include incorrect timing of prandial insulin administration, failure to administer basal insulin to persons with insulin deficiency/type 1 diabetes mellitus (DM), and inaccurate insulin dosing or timing resulting in hypoglycemia. Given the ongoing rapid assimilation of technology to manage our patients with DM, we investigated the use of continuous glucose monitoring (CGM) in the inpatient setting as a potential solution to traditional barriers to optimal hyperglycemia management for inpatient care. In this study, we evaluated the efficacy of use of inpatient CGM for insulin dosing in comparison with current standard of care and whether CGM could aid in minimizing hypoglycemic events. This study evaluated the use of Abbott professional (blinded) Freestyle Libre CGMs in participants treated with basal bolus insulin administered with subcutaneous insulin (basal bolus therapy [BBT]: n = 20) or on intravenous insulin (IVI) infusions (n =16) compared with standard point of care (POC) BG measurements. All participants on IVI were admitted with a diagnosis of diabetic ketoacidosis (DKA). The CGM data was not available in real time. Sensors were removed at the time of discharge and data uploaded to Libre View. Continuous BG data were aggregated for each subject and matched to POC BG or lab chemistry values within five minutes. The POC BG results were assessed for comparability (CGM vs standard BG testing). Data were further analyzed for clinical decision-making for correction insulin. The overall mean absolute relative difference including both IVI and BBT groups was 22.3% (SD, 9.0), with a median of 20.0%. By group, the IVI arm mean was 19.6% (SD, 9.4), with a median of 16.0%; for BBT, the arm mean was 24.6% (SD, 8.1), with a median 23.4%. Using the Wilcoxon two-sample test, the means were not different (P = .10), whereas the medians were (P = .015). The CGM consistently reported lower glucose values than POC BG in the majority of paired values (BBT arm mean difference = 44.8 mg/dL, IVI mean difference = 19.7 mg/dL). Glucose results were in agreement for the group 83% of the time with Bland-Altman Plot of Difference versus the mean of all glucometric data. Analysis of correction dose insulin using either CGM or POC BG values resulted in a negligible difference in calculated insulin dose recommended in those receiving subcutaneous insulin. Corrective doses were based on weight and insulin sensitivity (type 1 vs type 2 DM). Participants initially on IVI were included in a data set of BBT once IVI therapy ceased and basal bolus insulin regimen was started. The data of all basal bolus therapy participants with 1142 paired values of CGM versus POC glucose were used. The dosing difference was less for CGM than POC BG in the majority of paired values, and there was an absolute difference in dose of insulin of only 1.34 units. In the IVI group with 300 paired values of CGM versus POC glucose, there was an absolute difference in dose of insulin of only 0.74 units. About a third of the patients studied in the BBT arm experienced a hypoglycemic event with POC BG <70 mg/dL. If used in real time, CGM would have identified a hypoglycemic event for our patients on average 3 hours and 34 minutes before it was detected by standard POC BG. Two participants incurred severe nocturnal hypoglycemia during the study with POC BG <54 mg/dL with hypoglycemia detected on CGM up to 3 hours and 42 minutes before POC testing. These results suggest that the use of inpatient CGM arrives at similar correction insulin dosing. The routine use of CGM for inpatients would consistently underestimate the BG compared with POC BG and could aid in minimizing and predicting hypoglycemia in the hospital setting. Our data support that the model of adoption of real-time inpatient CGM technology is anticipated to have significant impact in the clinical setting in efforts to maintain adequate glycemic control targeting BG 140-180 mg/dL while minimizing the frequency of hypoglycemic events.

In this randomized, single blind, cross-over study 2.5 mg and 5 mg of the modified-release terbutaline formulation (SKP-1052) were compared with conventional immediate-release terbutaline (IRT, 5 mg) and placebo on overnight blood glucose (BG) and hypoglycaemia in 30 subjects with type 1 diabetes mellitus. Subjects received subcutaneous injections of insulin glargine (individualized doses) before dinner. SKP-1052, IRT or placebo was administered around 21:00 hours. BG and terbutaline concentrations were monitored overnight for 10 h post-dosing. Endpoints comprised of the nadir BG (BGn 0-10 h, primary endpoint), mean overnight BG (BGmean), morning BG (BGmorning) and hypoglycaemia rates as well as pharmacokinetic (PK) endpoints. SKP-1052 delayed release of terbutaline by 2 h [PK-tmax (mean ± SD) 5.0 ± 2.1 h (2.5 mg) and 4.7 ± 1.7 h (5 mg) vs. 2.6 ± 1.3 h with IRT, p < 0.01, respectively]. Compared with placebo, no significant differences were observed for BGn 0-10 h across treatments, but both 5 mg formulations showed less hypoglycaemic events [10 (IRT), 16 (SKP-1052) vs. 33], higher BGmean (120, 114 and 95 mg/dl) and BGmorning (126, 126 and 101 mg/dl, all comparisons p < 0.05 vs. placebo). Numerically higher BG-levels between 3 and 8 h post-dosing were observed with 2.5 mg SKP-1052 vs. placebo. Compared with IRT SKP-1052 delays release of terbutaline. 2.5 mg SKP-1052 led to numerically higher BG 3 to 8 h post-dose without fasting hyperglycaemia while 5 mg SKP-1052 resulted in fasting hyperglycaemia vs. placebo. Future studies will investigate optimized doses of SKP-1052 for nocturnal hypoglycaemia prevention.